Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aggressive lipid-lowering goals recommended by the second Adult Treatment Panel (ATP II) have created an increasing demand for treatment with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors. Fluvastatin is the first completely synthetic agent in this class and offers a considerable price advantage over the other HMG-CoA therapies. In May 1994, the Buffalo Veterans Affairs Medical Center Lipid Clinic adopted a fluvastatin-preferred program in which all patients who were recommended for an HMG-CoA reductase inhibitor would be treated with fluvastatin as a first-line agent. Fluvastatin was started at 20 mg daily and titrated to goal. Patients who were stable with other HMG-CoA reductase inhibitors were converted to fluvastatin as just described. Preliminary analysis shows that, for new patients, 20 mg of fluvastatin daily at bedtime reduced low density lipoprotein cholesterol (LDL-C) by an average of 22% (range, 5-32%). Preliminary results for patients converted from another HMG-CoA reductase inhibitor showed that fluvastatin produced an additional LDL-C reduction of 18% (range, 5-30%). With a daily dose of 20 mg fluvastatin, patients with no heart disease (primary prevention) achieved ATP II goals in 60% of cases. For patients with established heart disease (secondary prevention), the goals of ATP II are lower but, despite this, 30% of patients taking fluvastatin at 20 mg daily achieved these goals. The patients in both groups who failed to achieve ATP II goals were titrated to a 40 mg daily dose, but the results of this titration are not yet available. Pharmacoeconomic outcomes were favorable.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Outcome monitoring of fluvastatin in a Department of Veterans Affairs lipid clinic. 760 1

There appears to be little doubt that lowering serum cholesterol for reduction of risk for coronary artery disease (CAD) events in patients with established CAD is cost-effective and can decrease the rate of CAD events, stabilize atherosclerotic plaque progression, and reduce CAD mortality and all-cause mortality. Meta-analysis of clinical trials conducted in patients with CAD has shown a 26% reduction in CAD events and a 9% reduction in total mortality. It was generalized from the results of nine major, recent angiographically monitored clinical trials that an improvement in obstruction was seen in 8% of control patients and 25% of treated patients. In the recently released report of the second Adult Treatment Panel (ATP II) of the U.S. National Cholesterol Education Program, atherosclerotic disease status joins low-density lipoprotein cholesterol (LDL-C) level as central to the diagnosis and treatment algorithm. The ATP II evaluation process is divided into two categories according to whether atherosclerotic disease is present, and a lower LDL-C target level--100 mg/dL (2.6 mmol/L)--is set for secondary prevention. Initial therapy when LDL-C is > or = 100 mg/dL in a patient with atherosclerotic disease is the Step Two Diet, weight control, exercise, and control of other risk factors. Drug therapy may be considered after a relatively short trial of hygienic therapy if LDL-C remains > or = 130 mg/dL (3.4 mmol/L). Other, selected aspects of heart disease for general consideration in assessing CAD risk are family history and the presence of left ventricular hypertrophy (LVH). Family history of premature CAD is included in the ATP II algorithm, with different age considerations by gender added. Although LVH is not part of ATP II risk assessment, its presence as defined by echocardiography increases CAD risk six- to eightfold in both men and women.
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PMID:Heart disease in the assessment and treatment of hypercholesterolemia: coronary artery disease and other atherosclerotic disease, family history, and left ventricular hypertrophy. 801 74

Our purpose was to assess the efficacy and safety of intravenous ATP for the acute termination of paroxysmal supraventricular tachycardia. There were 14 women and 10 men, aged 38 +/- 15 years. Three patients had evidence of structural heart disease (Ebstein's anomaly associated to atrial septal defect, operated mitral stenosis with insertion of a mechanical heart valve and CAD respectively). Twelve patients had Wolff-Parkinson-White syndrome and another had undergone surgical ablation of an accessory pathway. At the time of electrophysiologic testing, ATP was administered during episodes of paroxysmal supraventricular tachycardia, via a central vein, in incremental doses of 5, 10 and 20 mg followed by a flush of 10 c.c. of isotonic saline. The mechanism of the arrhythmia was orthodromic AV reentrant tachycardia in 19 (79%), AV nodal reentrant tachycardia in 4 (16.6%) and atrial tachycardia in one patient. The mean frequency of the tachycardia was 174 +/- 33 b.p.m. A dose of 5 mg was effective in 16 patients (66%), 5 required 10 mg and two required 20 mg for termination of the tachycardia. In the patient with atrial tachycardia ATP was not effective. The average time after injection to termination of the arrhythmia was 16 +/- 8 seconds. Orthodromic AV reentrant tachycardia was interrupted in the AV node limb in all but one patient and AV nodal reentry was terminated in the "slow-pathway" in three of the four patients. Nine patients had premature ventricular complexes, isolated or in couplets, after the termination of the SVT. Three patients had immediate recurrence of the SVT.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Efficacy and safety of adenosine triphosphate in the control of supraventricular paroxysmal tachycardia]. 804 86

1. Exercise tolerance is impaired in congenital heart disease. To examine the possible contribution of abnormalities in skeletal muscle bioenergetics, we used 31P nuclear magnetic resonance spectroscopy to investigate muscle metabolism in 10 subjects with congenital heart disease with cyanosis (median age 17.3 years) and in eight healthy age-matched control subjects. Spectra were collected from the gastrocnemius muscle at rest and during exercise and recovery. 2. In resting muscle there were significant elevations in cytosolic pH and in the cytosolic concentration of inorganic phosphate in the patients, and a strong positive correlation between cytosolic pH and blood haemoglobin concentration in all subjects. 3. During plantar flexion exercise the patients showed increased phosphocreatine depletion and cytosolic acidification over a shorter duration of exercise. The rise in calculated cytosolic ADP concentration was similar in both groups. 4. After cessation of exercise, the recovery half-times of phosphocreatine, ADP and phosphate were two to three times longer in the patients, and the initial rate of phosphocreatine resynthesis (a measure of the rate of mitochondrial ATP synthesis) was half the control value, consistent with a reduction in the effective maximum rate of oxidative ATP synthesis (expressed per volume of muscle). Also, recovery was faster in the young control subjects than in our earlier studies of older healthy control subjects. 5. The high phosphate concentration in resting muscle and the abnormalities found in exercise and recovery are consistent with a decrease in oxidative ATP synthesis due to reduced oxygen delivery by the blood in chronic hypoxaemia. The correlation between cytosolic pH and haemoglobin concentration remains to be explained.
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PMID:Abnormalities in skeletal muscle metabolism in cyanotic patients with congenital heart disease: a 31P nuclear magnetic resonance spectroscopy study. 814 86

We use the hyperbolic relationship between cytosolic [ADP] and the rate of phosphocreatine (PCr) resynthesis after exercise to estimate the apparent maximum rate of oxidative ATP synthesis (QMAX). We examine data from some human diseases in which mitochondrial oxidation may be impaired (due to reduced mitochondrial numbers, intrinsic mitochondrial defect or impaired vascular supply). Muscle responds to impaired oxidation by stimulating anaerobic ATP synthesis and/or by increasing [ADP], the stimulus to the mitochondrion. However, these responses interact: [ADP] depends on pH and [PCr], and lactic acid production tends to lower [ADP] (by lowering pH), while proton efflux has the opposite effect. We identify four patterns of results: (A) in mitochondrial myopathy, apparent QMAX is reduced and [ADP] is appropriately increased, because increased proton efflux reduces the pH change in exercise despite increased lactic acid production; (B) in some conditions (e.g., cyanotic congenital heart disease) apparent QMAX is reduced but there is no compensatory rise in [ADP], probably because anaerobic ATP synthesis during exercise is increased without increase in proton efflux; (C) in other conditions (e.g., myotonic dystrophy) [ADP] is increased during exercise but apparent QMAX is normal, suggesting either an increase in proton efflux and/or decrease in anaerobic ATP synthesis during exercise; (D) there are also conditions (e.g., respiratory failure) where, despite impaired oxygen supply, both apparent QMAX and end-exercise [ADP] are normal. We also discuss the metabolic conditions under which end-exercise [ADP] is increased by a mitochondrial defect.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Quantitative analysis by 31P magnetic resonance spectroscopy of abnormal mitochondrial oxidation in skeletal muscle during recovery from exercise. 826 62

Normal adaptation to extra-uterine life consists of an immediate increase in endothelial and smooth muscle cell (SMC) surface: volume ratio as the cells 'spread' in the vessel wall. Lumen diameter increases and resistance falls. Changes in SMC shape are associated with a transient depolymerization of contractile and cytoskeletal filaments. The four SMC phenotypes identified in the vessel wall rapidly show postnatal changes in the types of filament proteins and contractile-associated proteins, indicating that the term 'differentiation' means little at this age. At birth, all SMCs have a predominantly synthetic phenotype. Endothelium-dependent relaxation is relatively poor despite abundant nitric oxide synthase. SMCs are relatively insensitive to nitric oxide despite a high basal generation and a stimulated increase in cGMP generation. By contrast, the relaxation in response to ATP-sensitive potassium (KATP) channel activation is present at birth, the response being similar to that seen in the adult. Neonatal pulmonary hypertension, due to either congenital heart disease or experimental chronic hypobaric hypoxia (51 kPa) is associated with abnormal structural remodelling. In experimental pulmonary hypertension, the normal maturation of endothelium-dependent and -independent relaxation via soluble guanylate cyclase is delayed in newborns and the established responses are inhibited in older animals. The relaxant response to KATP channel activation is preserved. Thus, adaptation to extra-uterine life consists of a rapid sequence of integrated morphological and functional changes, which is disturbed by the presence of pulmonary hypertension. The pattern of recovery from a pulmonary hypertensive insult is determined by the age at exposure and type and duration of the insult.
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PMID:Development of the normal and hypertensive pulmonary vasculature. 854 73

The aim of this manuscript is to review perturbations in bioenergetics that are redundant denominators in the diversity of factors mediating the pathogenesis and progression of coronary heart disease (CHD), congestive heart failure (CHF), hypertension and arrhythmias. This paper likewise assesses the pharmacodynamics of widely prescribed drugs that enhance cellular respiration, maintain positive inotropic, chronotropic, dromotropic cardiac effects, sustain myocardial biosynthesis, reverse the morbidity of heart disease, and assure low levels of toxicity commensurate with the agent's biocompatability. Conversely, it is essential to delineate the modality of xenobiotic drugs that inhibit energy transformations, enhance the pathogenesis of CHD, worsen survival in CHF, provoke arrhythmogenic effects, and induce serious side-effects. Documented evidence, derived from biochemical, physiological and pharmacological data sources, consistently links inhibited mitochondrial decarboxylation to aberrations in cholesterol metabolism, biosynthesis, and calcium balance. Underutilized citrates evolved from inhibited decarboxylation are degraded to acetyl CoA. The acetate is the source of steroid synthesis; its carbon atoms form the molecular basis for all endogenous cholesterol. Myocardial anoxia, a consequence of the atheromatous plaque, inhibits ATP production, impairs biosynthesis, induces negative cardiac inotropic and chronotropic effects, and enhances the pathogenesis of CHF. Inhibited decarboxylation is likewise a factor in the mobilization of in situ cardiac Ca2+, resulting in arrhythmias provoked by the cation's deficiency. The restoration of calcium homeostasis decreases peripheral vasotension, reducing hypertension. Parameters drawn from endocrinopathies and the new physiological dimension of microgravity are developed to illustrate the detrimental effect of inhibited bioenergetics on cardiac pathomorphism and cardiovascular dysfunction. In conclusion, anabolic agents, adjunctive to a productive life-style, can provide the rational basis for the prevention and treatment of cardiac diseases. Failure to understand mechanisms generating cardiovascular morbidity eventuates in ineffective and empirical treatment.
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PMID:Bioenergetics in the pathogenesis, progression and treatment of cardiovascular disorders. 858 65

Thirty-seven patients with ventricular tachyarrhythmias refractory to antiarrhythmic drug treatment, guided by electrophysiological testing, were submitted to implantation of a cardioverter-defibrillator by the transvenous technique. Mean age was 55 +/- 14 years and the underlying heart disease was coronary heart disease in 24 patients, cardiomyopathy or other etiologies in 11 patients. In 2 patients ventricular arrhythmias were idiopathic. Left ventricular ejection fraction was < or equal to 40% in 65% of the patients. The following devices were implanted: CPI Ventak P in 2 patients, Ventak P2 in 9 patients, Ventak PRx in 9 patients, Ventak PRxII in 2 patients, Telectronics Guardian ATP III 4215 in 9 patients, Siemens Siecure in 5 patients, Medtronic Jewel PCD in 1 patient. At implantation defibrillation threshold was lower with biphasic shocks than with monophasic shocks (17.0 +/- 3.2 vs 20.9 +/- 3.8 J, p < 0.003) and the need for subcutaneous patches was lower when biphasic shocks were employed. Operative and perioperative mortality were 0% and no significant complications were observed. During the follow-up (16 +/- 11 months) 35% of the patients had appropriate shocks and 93% of the patients with antitachycardia pacing availability (n = 15) had effective antitachycardia pacing interventions. The following complications were observed: lead failure in 4 patients (3 insulation breaks and 1 elongation for stretching), late lead dislodgement in 2 patients, lead recall in 1 patient, all of which required reintervention. Inappropriate shocks occurred in 30% of the patients and were related to lead failure, supraventricular arrhythmias or alternating current interference. During the follow-up one patient died of sudden death and one was submitted to heart transplantation. In conclusion, implantation of a cardioverter-defibrillator by the transvenous technique is a procedure relatively free from complications. During the follow-up lead failure appears to be one of the most relevant complications. Antitachycardia pacing allows effective termination of ventricular tachycardias without cardioversion, with a better compliance.
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PMID:[Transvenous cardioverter-defibrillators: clinical experience at implantation and follow-up]. 864 Aug 50

The ADP/ATP carrier is an autoantigen in myocarditis and dilated cardiomyopathy, both of which are diseases related to virus infections. Sera of these patients bear carrier-specific autoantibodies inhibiting transmembrane nucleotide transport on isolated mitochondria. To further assess the role of the ADP/ATP carrier in viral heart disease, guinea pigs were immunized with the isolated ADP/ATP carrier protein and A-strain mice were infected with coxsackie B3 virus. Both species generated specific and carrier-inactivating antibodies after immunization/infection. The transport activity of the ADP/ATP carrier-estimated from the cytosolic-mitochondrial difference of the phosphorylation potential of ATP (delta G[cyt-mit])-markedly declined in guinea pig and mice hearts. A close relationship was observed between the magnitude of reduction of delta G(cyt-mit) and the decrease of cardiac function. Therefore, it seems plausible that carrier dysfunction induced by viral infection creates an imbalance in myocardial energy metabolism, and is responsible for the impairment of cardiac function. The underlying mechanism might be an autoimmune reaction triggered via molecular mimicry or a modulation of the expression of ADP/ATP carrier isoforms changing the overall transport capacity of the cardiac ADP/ATP carrier.
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PMID:The role of the ADP/ATP carrier in the pathogenesis of viral heart disease. 868 5

The purpose of this study was to investigate the prevalence of hypercholesterolemia among subjects having diabetes and glucose intolerance, according to the guidelines of the National Cholesterol Education Program (Adult Treatment Panel II, ATP II). This survey consisted of 2090 subjects (856 men, 1234 women) aged 30 years or more from the Sun-Ming district of Kaohsiung city. Glucose tolerance status was ascertained for both medical history and a 75-g oral glucose tolerance test according to World Health Organization criteria. Frequency of elevated total cholesterol in female subjects with abnormal glucose tolerance is significantly greater than in those with normal glucose tolerance (NGT). However, only male subjects with undiagnosed NIDDM (UDDM) had a statistically higher rate of hypercholesterolemia than those with NGT. Of UDDM individuals, 68% have total cholesterol level between 200 and 239 mg/dl and two or more risk factors for heart disease or evidence of coronary heart disease or total cholesterol > or = 240 mg/dl or high-density lipoprotein (HDL) cholesterol < or = 35 mg/dl. Such individuals should have their low-density lipoprotein (LDL) cholesterol measured. Using the ATP II, LDL cholesterol levels warranting dietary treatment for hypercholesterolemia would be expected in 76% of UDDM. Due to the high prevalence of coronary heart disease in diabetic patients, investigation of blood lipid levels and coronary heart disease risk factors should be routine in these patients, and treatment strategies should include management of lipid disorders and the many other risk factors. A high frequency of dyslipidemia was found among UDDM group in our study. Early detection of undiagnosed diabetic patients is also very important in decreasing the prevalence of coronary heart disease.
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PMID:Hypercholesterolemia in undiagnosed non-insulin-dependent diabetes in southern Taiwan. 868 43


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